Are there non-linear relationships between alcohol consumption and long-term health? Protocol for a systematic review of observational studies employing approaches to improve causal inference

INTRODUCTION: There is a substantial literature finding that moderate alcohol consumption is protective against certain health conditions. However, more recent research has highlighted the possibility that these findings are methodological artefacts, caused by confounding and other biases. While modern analytical and study design approaches can mitigate confounding and thus enhance causal inference in observational studies, they are not routinely applied in research assessing the relationship between alcohol use and long-term health outcomes. The purpose of this systematic review is to identify observational studies that employ these analytical/design-based approaches in assessing whether relationships between alcohol consumption and health outcomes are non-linear. This review seeks to evaluate, on a per-outcome basis, what these studies find the strength and form of the relationship between alcohol consumption and health to be. METHODS AND ANALYSIS: Electronic databases (MEDLINE, PsycINFO, Embase and SCOPUS) were searched in May 2020. Study selection will comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles will be screened against eligibility criteria intended to capture studies using observational data to assess the relationship between varying levels of alcohol exposure and any long-term health outcome (actual or surrogate), and that have employed at least one of the prespecified approaches to enhancing causal inference. Risk of bias of included articles will be assessed using study design-specific tools. A narrative synthesis of the results is planned. ETHICS AND DISSEMINATION: Formal ethics approval is not required given there will be no primary data collection. The results of the study will be disseminated through published manuscripts, conferences and seminar presentations. PROSPERO REGISTRATION NUMBER: CRD42020185861.